This research will characterize the factors which initate and modulate inflammatory responses initiated by the immune system. In particular, the factors which mediate the accumulation of inflammatory cells such as polymorphonuclear leukocytes, macrophages and lymphocytes will be determined by using well defined animals models of acute and delayed hypersensitivity reactions in vivo. Materials isolated from inflammatory sites in vivo will be tested for chemotactic activity in vitro using modified Boyden chambers. Chemotatic factors will be purified and characterized and their kinetics of appearance and disappearance in vivo determined. Factors involved in the dissipation of inflammatory reactions will be isolated, characterized and their mechanism of action determined. The role of the inflammatory response in determining host susceptibility and resistance to endotoxin lethality will be defined and the mechanisms of host resistance to endotoxin determined. The role of adenosine deaminase in monocyte maturation and activation will be determined and the relationship between a deficiency of the enzyme to defective immune function will be explored. Immune effector function, including chemotactic responsiveness of polymorphonuclear leukocytes and monocytes as well as chemotactic lymphokine and complement-derived chemotactic factor production will be evaluated in patients with inflammatory conditions such as severe periodontal disease, rheumatoid arthritis and systemic lupus erythematosus to determine if abnormalities of specific components of the inflammatory response are related to disease expression.